Schizophrenia: the role of sleep and circadian rhythms in regulating dopamine and psychosis

Abstract

<jats:title>Abstract</jats:title><jats:p>Schizophrenia has long been associated with abnormalities in circadian rhythms and sleep. Up until now, there have been no thorough reviews of the potential mechanisms behind the myriad of circadian and sleep abnormalities observed in schizophrenia and psychosis. We present evidence of sleep playing an important role in psychosis predominantly mediated by dopaminergic pathways. A synthesis of both human and animal experimental work suggests that the interplay between sleep and dopamine is important in the generation and maintenance of psychosis. In particular, both animal and human data point to sleep disruption increasing dopamine release and sensitivity. Furthermore, elevated dopamine levels disrupt sleep and circadian rhythms. The synthesis of knowledge suggests that circadian rhythms, dopamine dysregulation, and psychosis are intricately linked. This suggests that treatment of circadian disturbance may be a useful target in improving the lives and symptoms of patients with schizophrenia.</jats:p>

Are sleep disturbances causally linked to the presence and severity of psychotic-like, dissociative and hypomanic experiences in non-clinical populations? A systematic review

“…However, the causal nature of sleep disturbances and these experiences are not currently known. This is despite multiple plausible theoretical routes through which sleep disturbances may exacerbate or induce psychotic-like, dissociative, and hypomanic experiences (Harvey et al, 2008;Yates, 2016;Pociavsek & Rowland, 2017). Sleep disturbances have been shown to negatively impact emotion regulation (Beattie et al, 2015), executive functioning (Tucker et al, 2010), increase threat anticipation at a behavioural (Kyle et al, 2014) and cortical level (Yoo et al, 2007;Baranger et al, 2017), and increase functional levels of dopamine (Yates, 2016).…”

Chronobiology Revisited in Psychiatric Disorders: From a Translational Perspective

“…Research into circadian abnormalities and sleep disruption in schizophrenia has attempted to explain the causal relationship in a reciprocal context. Hyperdopaminergia is a well-known phenomenon in psychosis syndromes and striatal hyperdopaminergic activity may be a result of sleep disruption and circadian abnormalities, and increased dopamine levels may induce sleep disruptions (Howes and Kapur, 2009;Monti et al, 2013;Yates, 2016). There is also supporting evidence showing an association between genetic polymorphisms and circadian disruption, which is consistently confirmed in animal models.…”

“…These findings may indicate a melatoninderived neurodevelopmental deficit at a cellular level (Galván-Arrieta et al, 2017). The absence of melatonin rhythmicity, decreased nocturnal secretion of melatonin, and phase advance in melatonin circadian rhythms have also been described in patients with schizophrenia (Rao et al, 1994;Anderson and Maes, 2012;Yates, 2016). Additionally, pineal calcification in computed tomography has been demonstrated in patients with schizophrenia, and this structural change has been found associated with cortical atrophy (Sandyk and Kay, 1991).…”

“…Melatonin is a versatile neuro-hormone that plays an important role in the pathophysiology of schizophrenia. 5-HT synthesis regulation, sleep-wake cycle, and anti-oxidant effects against neuroinflammation are impaired due to melatonin dysfunction in schizophrenia (Anderson and Maes, 2012;Yates, 2016). It has been shown that melatonin increases endogenous antioxidants by increasing phosphorylated glycogen synthase kinase-3 (GSK-3) levels and provides an anti-inflammatory effect (Olcese et al, 2009;Anderson and Maes, 2012).…”

Clocks in the clinic: circadian rhythms in health and disease

“…From a mechanistic perspective, a number of cellular and molecular processes have been identified to interact with the clock and modulate mood, including hypothalamic-pituitary-adrenal axis function, immune and neuroimmune processes, neurogenesis and direct control of neurotransmitter and neuromodulator systems 62. Circadian changes have also been described in a number of other psychiatric conditions, including schizophrenia,63 attention deficit hyperactivity disorder,64 obsessive compulsive disorder65 and borderline personality disorder 66. As such, circadian processes appear to be important transdiagnostic factors to consider in psychiatry and clinical psychology.…”